(1) a) Continued study of daily cortisol production rates (FPR) in patients and normal volunteers has revealed a number of significant findings. The value of FPR in normal volunteers (n = 11) is 9.6 plus or minus 2.6 mg/24 hrs (RSD = 27%) is both lower in absolute value and has a smaller range than determinations by other methods. The small range of values is consistent with the remarkably low variation observed in mean daily plasma cortisol concentration. (F) of 6 plus or minus 0.9 mu g/dl (RSD = 15%) determined by our isotope dilution methodology. FPR and (F) values are highly correlated in the normal volunteers. On the other hand, our results indicate substantial intersubject variation in metabolic clearance rate. MCR, of 176 plus or minus 95.9 I/day (RSD = 49%). There was no correlation between MCR and either FPR or (F) in the normal volunteers during any single sampling period; however, on a 24 hr basis, the relationship between MCR and FPR suggests that MCR is either unregulated or regulated by FPR rather than (F). b) All patients with Cushing's Syndrome (n = 6) demonstrated unequivocal elevation in FPR and loss of circadian rhythm. c) To date 16 studies of FPR have been performed in normal children. (2) To date four studies have been performed to determine testosterone production rate in women with polycystic ovarian disease. (3) Several alpha-carboxyamidated peptides that serve as models for peptide autocrine growth factors of small cell lung carcinoma have been characterized using a combination of peptidyl amino acid hydrolase and thermospray LC/MS. Preliminary work suggests that there is some ability to obtain sequence information from this approach.